Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 62 Records) |
Query Trace: Angulo F [original query] |
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Food and Drug Administration public workshop summary-development considerations of antifungal drugs to address unmet medical need
Yasinskaya Y , Bala S , Waack U , Dixon C , Higgins K , Moore JN , Jjingo CJ , O'Shaughnessy E , Colangelo P , Botgros R , Nambiar S , Angulo D , Dane A , Chiller T , Hodges MR , Sandison T , Hope W , Walsh TJ , Pappas P , Katragkou A , Kovanda L , Rex JH , Marr KA , Ostrosky-Zeichner L , Sekine S , Deshpande M , Shukla SJ , Farley J . Clin Infect Dis 2023 77 (3) 380-387 Pressing challenges in the treatment of invasive fungal infections (IFI) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics; clinical trial endpoints; prolonged trial duration; difficulties in patient recruitment, including subpopulations (e.g., pediatrics); and heterogeneity of the IFIs. On August 4, 2020, the U.S. Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This paper summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development. |
Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections.
Ghannoum M , Arendrup MC , Chaturvedi VP , Lockhart SR , McCormick TS , Chaturvedi S , Berkow EL , Juneja D , Tarai B , Azie N , Angulo D , Walsh TJ . Antibiotics (Basel) 2020 9 (9) Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections. |
Can we make human plague history A call to action
Baril L , Valles X , Stenseth NC , Rajerison M , Ratsitorahina M , Pizarro-Cerda J , Demeure C , Belmain S , Scholz H , Girod R , Hinnebusch J , Vigan-Womas I , Bertherat E , Fontanet A , Yazadanpanah Y , Carrara G , Deuve J , D'Ortenzio E , Angulo JOC , Mead P , Horby PW . BMJ Glob Health 2019 4 (6) e001984 In spite of the historical capacity to disrupt human societies, plague is currently a neglected disease. | | Given the resilience to be controlled in the wild, the focus should be put to prevent human transmission of plague. | | Research priorities include new diagnostic and therapeutic tools which are urgently needed, especially to deal with the pulmonary form of plague. | | A cross-disciplinary research approach is needed, including basic, ecological, clinical and social sciences. |
In vitro activity of ibrexafungerp, a novel glucan synthase inhibitor against Candida glabrata isolates with FKS mutations
Nunnally NS , Etienne KA , Angulo D , Lockhart SR , Berkow EL . Antimicrob Agents Chemother 2019 63 (11) Ibrexafungerp is a first in class glucan-synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, and micafungin) by broth microdilution. Results for ibrexafungerp were compared to those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant Candida glabrata isolates. |
Ten years of global disease detection and counting: Program accomplishments and lessons learned in building global health security
Montgomery JM , Woolverton A , Hedges S , Pitts D , Alexander J , Ijaz K , Angulo F , Dowell S , Katz R , Henao O . BMC Public Health 2019 19 510 Worldwide, infectious diseases continue to emerge at an alarming pace, due to numerous factors including microbial adaptation, increasing human population migration, urbanization, conflict and instability, intensified animal-human interface, and habitat perturbation [1,2,3,4,5,6]. The litmus test for an effective national public health program is its ability to be ready to initiate an effective response for an unknown emerging or re-emerging infectious disease or public health event. The most impactful global health programs are built with the understanding that they must be able to help countries strengthen core public health capacity so that new threats can be detected and contained before they become international crises that increase morbidity and mortality, adversely impact the health and livelihoods of individuals and populations, disrupt travel, interfere with global trade and economies, or even lead to political destabilization [6, 7]. |
Building global health security capacity: The role for implementation science
Morgan J , Kennedy ED , Pesik N , Angulo FJ , Craig AS , Knight NW , Bunnell RE . Health Secur 2018 16 S5-s7 Since the launch of the Global Health Security Agenda (GHSA) in 2014,1-3 many countries around the world have accelerated efforts to achieve compliance with the World Health Organization's (WHO) International Health Regulations (IHR 2005) to build their capacities to detect, assess, and report public health events.4 WHO approved a standardized Joint External Evaluation (JEE) tool in February 2016 that provides a framework for assessing a country's gaps and progress toward IHR 2005 implementation.5,6 By October 2018, more than 86 countries in 6 regions had completed a JEE.7 Based on JEE scores and recommended priority actions for improvement, multiple countries, in collaboration with technical partners such as the US Centers for Disease Control and Prevention (CDC), are actively working to build their capacities and strengthen core systems to prevent, detect, and respond to public health threats. |
Unintended consequences associated with national-level restrictions on antimicrobial use in food-producing animals
McEwen SA , Angulo FJ , Collignon PJ , Conly JM . Lancet Planet Health 2018 2 (7) e279-e282 Among actions needed to address the antimicrobial resistance crisis are restrictions on the use of medically important antimicrobials in food-producing animals, which are often administered through national-level policy. One example is the complete restriction of antimicrobials for growth promotion, as recommended in WHO guidelines on use of medically important antimicrobials in food-producing animals.1 The obvious intended consequence is reduced antimicrobial resistance but there could also be unintended consequences, such as harm to animal health and added cost of production. Some people in the agriculture sector fear serious consequences which deters implementation of the needed restrictions. We reviewed the published evidence on unintended consequences associated with national-level restrictions. We used keyword searches in Ovid MEDLINE and AGRICOLA databases to identify interventional or observational studies that reported national-level restriction of antimicrobial use in food animals, and compared non-antimicrobial resistance outcomes between intervention and comparator groups in food animals or in humans. Eligible antimicrobial use restrictions included mandatory or voluntary prohibition of antimicrobial use, limitations on specific drug classes, and incentives for reduced antimicrobial use. The search identified 14 articles, all from Europe (table). |
Risk for interspecies transmission of zoonotic pathogens during poultry processing and pork production in Peru: A qualitative study
Carnero AM , Kitayama K , Diaz DA , Garvich M , Angulo N , Cama VA , Gilman RH , Bayer AM . Zoonoses Public Health 2018 65 (5) 528-539 Interspecies transmission of pathogens is an unfrequent but naturally occurring event and human activities may favour opportunities not previously reported. Reassortment of zoonotic pathogens like influenza A virus can result from these activities. Recently, swine and birds have played a central role as "mixing vessels" for epidemic and pandemic events related to strains like H1N1 and H5N1. Unsafe practices in poultry markets and swine farms can lead to interspecies transmission, favouring the emergence of novel strains. Thus, understanding practices that lead to interspecies interactions is crucial. This qualitative study aimed to evaluate poultry processing practices in formal and informal markets and the use of leftovers by swine farmers in three Peruvian cities: Lima (capital), Tumbes (coastal) and Tarapoto (jungle). We conducted 80 direct observations at formal and informal markets and interviewed 15 swine farmers. Processors slaughter and pluck chickens and vendors and/or processors eviscerate chickens. Food safety and hygiene practices were suboptimal or absent, although some heterogeneity was observed between cities and chicken vendors versus processors. Both vendors (76%) and processors (100%) sold the chicken viscera leftovers to swine farmers, representing the main source of chicken viscera for swine farms (53%). Swine farmers fed the chicken viscera to their swine. Chicken viscera cooking times varied widely and were insufficient in some cases. Non-abattoired poultry leads to the sale of poultry leftovers to small-scale swine farms, resulting in indirect but frequent interspecies contacts that can lead to interspecies transmission of bacterial pathogens or the reassortment of influenza A viruses. These interactions are exacerbated by suboptimal safety and hygiene conditions. People involved in these activities constitute an at-risk population who could play a central role in preventing the transmission of pathogens between species. Educational interventions on hygiene and food safety practices will be important for reducing the risk of interspecies influenza transmission. |
Progress and opportunities for strengthening global health security
Angulo FJ , Cassell CH , Tappero JW , Bunnell RE . Emerg Infect Dis 2017 23 (13) S1-S4 In today’s interconnected world, an infectious disease outbreak that is not rapidly detected and controlled at its source can become a costly global health threat, both in lives lost and economic turmoil (1,2). Every year, thousands of outbreaks occur worldwide, many of which involve pathogens with pandemic potential. Since 2009, the World Health Organization (WHO) has declared public health emergencies of international concern for outbreaks of influenza A(H1N1) in 2009, Ebola in West Africa in 2014, and Zika in the Americas in 2015 (2). In 2007, the International Health Regulations 2005 (IHR 2005) entered into force, and all 196 state parties were legally bound to implement the core capacity required under the regulations. However, in 2014, almost two thirds of member states reported not being in compliance (3). To accelerate progress toward IHR 2005 compliance, the Global Health Security Agenda (GHSA) was launched by 29 countries, WHO, the Food and Agriculture Organization of the United Nations, and the World Organisation for Animal Health in 2014 and now includes >60 nations (4). |
Surveillance training for Ebola preparedness in Cote d'Ivoire, Guinea-Bissau, Senegal, and Mali
Caceres VM , Sidibe S , Andre M , Traicoff D , Lambert S , King M , Kazambu D , Lopez A , Pedalino B , Guibert DJH , Wassawa P , Cardoso P , Assi B , Ly A , Traore B , Angulo FJ , Quick L . Emerg Infect Dis 2017 23 (13) S174-82 The 2014-2015 epidemic of Ebola virus disease in West Africa primarily affected Guinea, Liberia, and Sierra Leone. Several countries, including Mali, Nigeria, and Senegal, experienced Ebola importations. Realizing the importance of a trained field epidemiology workforce in neighboring countries to respond to Ebola importations, the Centers for Disease Control and Prevention Field Epidemiology Training Program unit implemented the Surveillance Training for Ebola Preparedness (STEP) initiative. STEP was a mentored, competency-based initiative to rapidly build up surveillance capacity along the borders of the at-risk neighboring countries Cote d'Ivoire, Mali, Senegal, and Guinea-Bissau. The target audience was district surveillance officers. STEP was delivered to 185 participants from 72 health units (districts or regions). Timeliness of reporting and the quality of surveillance analyses improved 3 months after training. STEP demonstrated that mentored, competency-based training, where learners attain competencies while delivering essential public health services, can be successfully implemented in an emergency response setting. |
US Centers for Disease Control and Prevention and its partners' contributions to global health security
Tappero JW , Cassell CH , Bunnell RE , Angulo FJ , Craig A , Pesik N , Dahl BA , Ijaz K , Jafari H , Martin R . Emerg Infect Dis 2017 23 (13) S5-S14 To achieve compliance with the revised World Health Organization International Health Regulations (IHR 2005), countries must be able to rapidly prevent, detect, and respond to public health threats. Most nations, however, remain unprepared to manage and control complex health emergencies, whether due to natural disasters, emerging infectious disease outbreaks, or the inadvertent or intentional release of highly pathogenic organisms. The US Centers for Disease Control and Prevention (CDC) works with countries and partners to build and strengthen global health security preparedness so they can quickly respond to public health crises. This report highlights selected CDC global health protection platform accomplishments that help mitigate global health threats and build core, cross-cutting capacity to identify and contain disease outbreaks at their source. CDC contributions support country efforts to achieve IHR 2005 compliance, contribute to the international framework for countering infectious disease crises, and enhance health security for Americans and populations around the world. |
World Health Organization (WHO) guidelines on use of medically important antimicrobials in food-producing animals
Aidara-Kane A , Angulo FJ , Conly JM , Minato Y , Silbergeld EK , McEwen SA , Collignon PJ . Antimicrob Resist Infect Control 2018 7 7 Background: Antimicrobial use in food-producing animals selects for antimicrobial resistance that can be transmitted to humans via food or other transmission routes. The World Health Organization (WHO) in 2005 ranked the medical importance of antimicrobials used in humans. In late 2017, to preserve the effectiveness of medically important antimicrobials for humans, WHO released guidelines on use of antimicrobials in food-producing animals that incorporated the latest WHO rankings. Methods: WHO commissioned systematic reviews and literature reviews, and convened a Guideline Development Group (GDG) of external experts free of unacceptable conflicts-of-interest. The GDG assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and formulated recommendations using a structured evidence-to-decision approach that considered the balance of benefits and harms, feasibility, resource implications, and impact on equity. The resulting guidelines were peer-reviewed by an independent External Review Group and approved by the WHO Guidelines Review Committee. Results: These guidelines recommend reductions in the overall use of medically important antimicrobials in food-producing animals, including complete restriction of use of antimicrobials for growth promotion and for disease prevention (i.e., in healthy animals considered at risk of infection). These guidelines also recommend that antimicrobials identified as critically important for humans not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option. Conclusions: To preserve the effectiveness of medically important antimicrobials, veterinarians, farmers, regulatory agencies, and all other stakeholders are urged to adopt these recommendations and work towards implementation of these guidelines. |
Illustrative examples of probable transfer of resistance determinants from food animals to humans: Streptothricins, glycopeptides, and colistin
Webb HE , Angulo FJ , Granier SA , Scott HM , Loneragan GH . F1000Res 2017 6 1805 Use, overuse, and misuse of antimicrobials contributes to selection and dissemination of bacterial resistance determinants that may be transferred to humans and constitute a global public health concern. Because of the continued emergence and expansion of antimicrobial resistance, combined with the lack of novel antimicrobial agents, efforts are underway to preserve the efficacy of current available life-saving antimicrobials in humans. As a result, uses of medically important antimicrobials in food animal production have generated debate and led to calls to reduce both antimicrobial use and the need for use. This manuscript, commissioned by the World Health Organization (WHO) to help inform the development of the WHO guidelines on the use of medically important antimicrobials in food animals, includes three illustrations of antimicrobial use in food animal production that has contributed to the selection-and subsequent transfer-of resistance determinants from food animals to humans. Herein, antimicrobial use and the epidemiology of bacterial resistance are described for streptothricins, glycopeptides, and colistin. Taken together, these historical and current narratives reinforce the need for actions that will preserve the efficacy of antimicrobials. |
Attribution of global foodborne disease to specific foods: Findings from a World Health Organization structured expert elicitation
Hoffmann S , Devleesschauwer B , Aspinall W , Cooke R , Corrigan T , Havelaar A , Angulo F , Gibb H , Kirk M , Lake R , Speybroeck N , Torgerson P , Hald T . PLoS One 2017 12 (9) e0183641 BACKGROUND: Recently the World Health Organization, Foodborne Disease Burden Epidemiology Reference Group (FERG) estimated that 31 foodborne diseases (FBDs) resulted in over 600 million illnesses and 420,000 deaths worldwide in 2010. Knowing the relative role importance of different foods as exposure routes for key hazards is critical to preventing illness. This study reports the findings of a structured expert elicitation providing globally comparable food source attribution estimates for 11 major FBDs in each of 14 world subregions. METHODS AND FINDINGS: We used Cooke's Classical Model to elicit and aggregate judgments of 73 international experts. Judgments were elicited from each expert individually and aggregated using both equal and performance weights. Performance weighted results are reported as they increased the informativeness of estimates, while retaining accuracy. We report measures of central tendency and uncertainty bounds on food source attribution estimate. For some pathogens we see relatively consistent food source attribution estimates across subregions of the world; for others there is substantial regional variation. For example, for non-typhoidal salmonellosis, pork was of minor importance compared to eggs and poultry meat in the American and African subregions, whereas in the European and Western Pacific subregions the importance of these three food sources were quite similar. Our regional results broadly agree with estimates from earlier European and North American food source attribution research. As in prior food source attribution research, we find relatively wide uncertainty bounds around our median estimates. CONCLUSIONS: We present the first worldwide estimates of the proportion of specific foodborne diseases attributable to specific food exposure routes. While we find substantial uncertainty around central tendency estimates, we believe these estimates provide the best currently available basis on which to link FBDs and specific foods in many parts of the world, providing guidance for policy actions to control FBDs. |
In vitro activity of a novel glucan synthase inhibitor, SCY-078, against clinical isolates of Candida auris
Berkow EL , Angulo D , Lockhart SR . Antimicrob Agents Chemother 2017 61 (7) Candida auris, an emerging fungal pathogen that is associated with high mortality, has been identified in many countries across the world..... |
Clinical and microbiological features of invasive nontyphoidal Salmonella associated with HIV-infected patients, Gauteng Province, South Africa
Keddy KH , Musekiwa A , Sooka A , Karstaedt A , Nana T , Seetharam S , Nchabaleng M , Lekalakala R , Angulo FJ , Klugman KP . Medicine (Baltimore) 2017 96 (13) e6448 The aim of this study was to define factors associated with HIV-infected versus uninfected patients with invasive nontyphoidal Salmonella (iNTS) and factors associated with mortality, which are inadequately described in Africa.Laboratory-based surveillance for iNTS was undertaken. At selected sentinel sites, clinical data (age, sex, HIV status, severity of illness, and outcome) were collected.Surveillance was conducted in Gauteng, South Africa, from 2003 to 2013. Clinical and microbiological differences between HIV-infected and uninfected patients were defined and risk factors for mortality established.Of 4886 iNTS infections in Gauteng from 2003 to 2013, 3106 (63.5%) were diagnosed at sentinel sites. Among persons with iNTS infections, more HIV-infected persons were aged ≥5 years (chi = 417.6; P < 0.001) and more HIV-infected children were malnourished (chi = 5.8; P = 0.02). Although 760 (30.6%) patients died, mortality decreased between 2003 [97/263 (36.9%)] and 2013 [926/120 (21.7%)]. On univariate analysis, mortality was associated with patients aged 25 to 49 years [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.7-2.7; P < 0.001 and ≥50 years (OR = 3.0; 95% CI = 2.2-4.1; P < 0.001) compared with children < 5 years, HIV-infected patients (OR = 2.4; 95% CI = 1.7-3.4; P < 0.001), and severe illness (OR = 5.4; 95% CI = 3.6-8.1; P < 0.001). On multivariate analysis, mortality was associated with patients aged ≥50 years [adjusted OR (AOR) = 3.6, 95% CI = 2.1-6.1, P < 0.001] and severe illness (AOR = 6.3; 95% CI = 3.8-10.5; P < 0.001).Mortality due to iNTS in Gauteng remains high primarily due to disease severity. Interventions must be aimed at predisposing conditions, including HIV, other immune-suppressive conditions, and malignancy. |
An association between decreasing incidence of invasive non-typhoidal salmonellosis and increased use of antiretroviral therapy, Gauteng Province, South Africa, 2003-2013
Keddy KH , Takuva S , Musekiwa A , Puren AJ , Sooka A , Karstaedt A , Klugman KP , Angulo FJ . PLoS One 2017 12 (3) e0173091 BACKGROUND: HIV-infected persons are at increased risk of opportunistic infections, including invasive nontyphoidal Salmonella (iNTS) infections; antiretroviral therapy (ART) reduces this risk. We explored changing iNTS incidence associated with increasing ART availability in South Africa. METHODS: Laboratory-based surveillance for iNTS was conducted in Gauteng Province, South Africa, with verification using the National Health Laboratory Service's Central Data Warehouse (CDW), between 2003 and 2013. Isolates were serotyped at the Centre for Enteric Diseases. CDW data on patient numbers obtaining HIV viral load measurements provided estimates of numbers of HIV-infected patients receiving ART. A Poisson regression model was used to measure the changing incidence of iNTS infection from 2003 to 2013. The correlation between the incidence of iNTS and ART use from 2004 to 2013 was determined using Pearson's correlation coefficient. RESULTS: From 2003-2013, the incidence of iNTS per 100,000 population per year decreased from 5.0 to 2.2 (p < .001). From 2004 to 2013, the incidence per 100,000 population of HIV viral load testing increased from 75.2 to 3,620.3 (p < .001). The most common serotypes causing invasive disease were Salmonella enterica serovar Typhimurium (Salmonella Typhimurium), and Salmonella Enteritidis: 2,469 (55.4%) and 1,156 (25.9%) of 4,459 isolates serotyped, respectively. A strong negative correlation was observed between decreasing iNTS incidence and increasing ART use from 2004 to 2013 (r = -0.94, p < .001). Similarly, decreasing incidence of invasive Salmonella Typhimurium infection correlated with increasing ART use (r = -0.93, p < .001). Incidence of invasive Salmonella Enteritidis infection increased, however (r = 0.95, p < .001). Between 2003 and 2004, fewer adult men than women presented with iNTS (male-to-female rate ratio 0.73 and 0.89, respectively). This was reversed from 2005 through 2013 (ranging from 1.07 in 2005 to 1.44 in 2013). Adult men accessed ART less (male-to-female rate ratio ranging from 0.61 [2004] to 0.67 [2013]). CONCLUSIONS: The incidence of iNTS infections including Salmonella Typhimurium decreased significantly in Gauteng Province in association with increased ART utilization. Adult men accessed ART programs less than women, translating into increasing iNTS incidence in this group. Monitoring iNTS incidence may assist in monitoring the ART program. Increasing incidence of invasive Salmonella Enteritidis infections needs further elucidation. |
Diarrhoeal disease in children due to contaminated food
Kirk MD , Angulo FJ , Havelaar AH , Black RE . Bull World Health Organ 2017 95 (3) 233-234 In December 2015, the World Health Organization (WHO) released estimates of the burden of human disease attributable to consumption of food contaminated with 31 infectious agents or chemicals.1 The report concluded that exposure to contaminated food worldwide in 2010 resulted in 600 million episodes of illness (95% uncertainty interval, UI: 420–960 million), 420 000 deaths (95% UI: 310 000–600 000) and 33 million disability-adjusted life years (DALYs) (95% UI: 25–46 million).1 The numbers were based on 4.6 billion cases of diarrhoea (95% UI: 3.5–6.5 billion) and 1.6 million deaths due to diarrhoea (95% UI: 1.3–1.9 million) that occurred worldwide in 2010, similar to numbers occurring in later years.2 | A key element of the estimation was attributing a proportion of the diarrhoea deaths to foodborne transmission of infections. A structured expert judgement was used to apportion transmission modes for individual pathogens, by estimating that 29% (95% UI: 22–36%) of 11 key bacterial, viral and protozoal causes of diarrhoea were foodborne.3 Food contaminated with these 11 agents resulted in 548 million episodes of diarrhoea (95% UI: 370–888 million) and 200 000 deaths (95% UI: 137 000–287 000) in 2010. Of these, 217 million infections (39%; 95% UI: 29–38%) were in children younger than 5 years of age.4 This disproportionate burden of foodborne diarrhoeal disease in young children is evident in the high rate ratio of DALYs in children younger than 5 years compared with older children and adults (ratio: 11.6; 95% UI: 8.4–15.6). Among children younger than 5 years, foodborne transmission of the 11 agents could have constituted as much as 16% of the estimated 578 000 deaths due to diarrhoea (95% UI: 448 000–750 000), updated to 2013.5 |
Typhoid fever in South Africa in an endemic HIV setting
Keddy KH , Sooka A , Smith AM , Musekiwa A , Tau NP , Klugman KP , Angulo FJ . PLoS One 2016 11 (10) e0164939 BACKGROUND: Typhoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high. METHODS AND FINDINGS: Nationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003-2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3-50.3) and disease severity (AOR 9.8; 95% CI 1.6-60.0) on multivariate analysis. CONCLUSIONS: Typhoid fever incidence in South Africa was largely unchanged from 2003-2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults. |
Early identification and prevention of the spread of Ebola in high-risk African countries
Breakwell L , Gerber AR , Greiner AL , Hastings DL , Mirkovic K , Paczkowski MM , Sidibe S , Banaski J , Walker CL , Brooks JC , Caceres VM , Arthur RR , Angulo FJ . MMWR Suppl 2016 65 (3) 21-7 In the late summer of 2014, it became apparent that improved preparedness was needed for Ebola virus disease (Ebola) in at-risk countries surrounding the three highly affected West African countries (Guinea, Sierra Leone, and Liberia). The World Health Organization (WHO) identified 14 nearby African countries as high priority to receive technical assistance for Ebola preparedness; two additional African countries were identified at high risk for Ebola introduction because of travel and trade connections. To enhance the capacity of these countries to rapidly detect and contain Ebola, CDC established the High-Risk Countries Team (HRCT) to work with ministries of health, CDC country offices, WHO, and other international organizations. From August 2014 until the team was deactivated in May 2015, a total of 128 team members supported 15 countries in Ebola response and preparedness. In four instances during 2014, Ebola was introduced from a heavily affected country to a previously unaffected country, and CDC rapidly deployed personnel to help contain Ebola. The first introduction, in Nigeria, resulted in 20 cases and was contained within three generations of transmission; the second and third introductions, in Senegal and Mali, respectively, resulted in no further transmission; the fourth, also in Mali, resulted in seven cases and was contained within two generations of transmission. Preparedness activities included training, developing guidelines, assessing Ebola preparedness, facilitating Emergency Operations Center establishment in seven countries, and developing a standardized protocol for contact tracing. CDC's Field Epidemiology Training Program Branch also partnered with the HRCT to provide surveillance training to 188 field epidemiologists in Cote d'Ivoire, Guinea-Bissau, Mali, and Senegal to support Ebola preparedness. Imported cases of Ebola were successfully contained, and all 15 priority countries now have a stronger capacity to rapidly detect and contain Ebola.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). |
Incident management systems and building emergency management capacity during the 2014-2016 Ebola epidemic - Liberia, Sierra Leone, and Guinea
Brooks JC , Pinto M , Gill A , Hills KE , Murthy S , Podgornik MN , Hernandez LF , Rose DA , Angulo FJ , Rzeszotarski P . MMWR Suppl 2016 65 (3) 28-34 Establishing a functional incident management system (IMS) is important in the management of public health emergencies. In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC established the Emergency Management Development Team (EMDT) to coordinate technical assistance for developing emergency management capacity in Guinea, Liberia, and Sierra Leone. EMDT staff, deployed staff, and partners supported each country to develop response goals and objectives, identify gaps in response capabilities, and determine strategies for coordinating response activities. To monitor key programmatic milestones and assess changes in emergency management and response capacities over time, EMDT implemented three data collection methods in country: coordination calls, weekly written situation reports, and an emergency management dashboard tool. On the basis of the information collected, EMDT observed improvements in emergency management capacity over time in all three countries. The collaborations in each country yielded IMS structures that streamlined response and laid the foundation for long-term emergency management programs.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html). |
Emergency response in a global health crisis: epidemiology, ethics, and Ebola application
Salerno J , Hlaing WM , Weiser T , Striley C , Schwartz L , Angulo FJ , Neslund VS . Ann Epidemiol 2016 26 (4) 234-7 PURPOSE: The link between ethics and epidemiology can go unnoticed in contemporary gatherings of professional epidemiologists or trainees at conferences and workshops, as well as in teaching. Our goal is to provide readers with information about the activities of the College and to provide a broad perspective on a recent major issue in epidemiology. METHODS: The Ethics Committee of the American College of Epidemiology (ACE) presented a plenary session at the 2015 Annual Meeting in Atlanta, GA, on the complexities of ethics and epidemiology in the context of the 2014-2015 Ebola virus disease outbreak and response in West Africa. This article presents a summary and further discussion of that plenary session. RESULTS: Three main topic areas were presented: clinical trials and ethics in public health emergencies, public health practice, and collaborative work. A number of key ethical concepts were highlighted and discussed in relation to Ebola and the ACE Ethics Guidelines. CONCLUSIONS: The Ebola virus disease outbreak is an example of a public health humanitarian crisis from which we hope to better understand the role of professional epidemiologists in public health practice and research and recognize ethical challenges epidemiologists faced. |
World Health Organization estimates of the relative contributions of food to the burden of disease due to selected foodborne hazards: a structured expert elicitation
Hald T , Aspinall W , Devleesschauwer B , Cooke R , Corrigan T , Havelaar AH , Gibb HJ , Torgerson PR , Kirk MD , Angulo FJ , Lake RJ , Speybroeck N , Hoffmann S . PLoS One 2016 11 (1) e0145839 BACKGROUND: The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization (WHO) to estimate the global burden of foodborne diseases (FBDs). This estimation is complicated because most of the hazards causing FBD are not transmitted solely by food; most have several potential exposure routes consisting of transmission from animals, by humans, and via environmental routes including water. This paper describes an expert elicitation study conducted by the FERG Source Attribution Task Force to estimate the relative contribution of food to the global burden of diseases commonly transmitted through the consumption of food. METHODS AND FINDINGS: We applied structured expert judgment using Cooke's Classical Model to obtain estimates for 14 subregions for the relative contributions of different transmission pathways for eleven diarrheal diseases, seven other infectious diseases and one chemical (lead). Experts were identified through international networks followed by social network sampling. Final selection of experts was based on their experience including international working experience. Enrolled experts were scored on their ability to judge uncertainty accurately and informatively using a series of subject-matter specific 'seed' questions whose answers are unknown to the experts at the time they are interviewed. Trained facilitators elicited the 5th, and 50th and 95th percentile responses to seed questions through telephone interviews. Cooke's Classical Model uses responses to the seed questions to weigh and aggregate expert responses. After this interview, the experts were asked to provide 5th, 50th, and 95th percentile estimates for the 'target' questions regarding disease transmission routes. A total of 72 experts were enrolled in the study. Ten panels were global, meaning that the experts should provide estimates for all 14 subregions, whereas the nine panels were subregional, with experts providing estimates for one or more subregions, depending on their experience in the region. The size of the 19 hazard-specific panels ranged from 6 to 15 persons with several experts serving on more than one panel. Pathogens with animal reservoirs (e.g. non-typhoidal Salmonella spp. and Toxoplasma gondii) were in general assessed by the experts to have a higher proportion of illnesses attributable to food than pathogens with mainly a human reservoir, where human-to-human transmission (e.g. Shigella spp. and Norovirus) or waterborne transmission (e.g. Salmonella Typhi and Vibrio cholerae) were judged to dominate. For many pathogens, the foodborne route was assessed relatively more important in developed subregions than in developing subregions. The main exposure routes for lead varied across subregions, with the foodborne route being assessed most important only in two subregions of the European region. CONCLUSIONS: For the first time, we present worldwide estimates of the proportion of specific diseases attributable to food and other major transmission routes. These findings are essential for global burden of FBD estimates. While gaps exist, we believe the estimates presented here are the best current source of guidance to support decision makers when allocating resources for control and intervention, and for future research initiatives. |
Aetiology-specific estimates of the global and regional incidence and mortality of diarrhoeal diseases commonly transmitted through food
Pires SM , Fischer-Walker CL , Lanata CF , Devleesschauwer B , Hall AJ , Kirk MD , Duarte AS , Black RE , Angulo FJ . PLoS One 2015 10 (12) e0142927 BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1-3.3 billion) cases and 599,000 (95% UI 472,000-802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468-1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154-380 million), Shigella spp. (188 million; 95% UI 94-379 million) and Giardia lamblia (179 million; 95% UI 125-263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783-266,561), enteropathogenic E. coli (121,455; 95% UI 103,657-143,348), ETEC (73,041; 95% UI 55,474-96,984) and Shigella (64,993; 95% UI 48,966-92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods. |
World Health Organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: a data synthesis
Torgerson PR , Devleesschauwer B , Praet N , Speybroeck N , Willingham AL , Kasuga F , Rokni MB , Zhou XN , Fevre EM , Sripa B , Gargouri N , Furst T , Budke CM , Carabin H , Kirk MD , Angulo FJ , Havelaar A , de Silva N . PLoS Med 2015 12 (12) e1001920 BACKGROUND: Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food. METHODS AND FINDINGS: Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4-79.0 million) and 59,724 (95% UI 48,017-83,616) deaths annually resulting in 8.78 million (95% UI 7.62-12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2-38.1 million) cases and 45,927 (95% UI 34,763-59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61-8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29-22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40-14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14-3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65-2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000-1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi). CONCLUSIONS: Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations. |
World Health Organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis
Kirk MD , Pires SM , Black RE , Caipo M , Crump JA , Devleesschauwer B , Dopfer D , Fazil A , Fischer-Walker CL , Hald T , Hall AJ , Keddy KH , Lake RJ , Lanata CF , Torgerson PR , Havelaar AH , Angulo FJ . PLoS Med 2015 12 (12) e1001921 BACKGROUND: Foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases. METHODS AND FINDINGS: We synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990-2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5-2.9 billion) cases, over one million (95% UI 0.89-1.4 million) deaths, and 78.7 million (95% UI 65.0-97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23-36%) of cases caused by diseases in our study, or 582 million (95% UI 401-922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5-37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70-251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52-177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49-6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne. CONCLUSIONS: Foodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings. |
World Health Organization global estimates and regional comparisons of the burden of foodborne disease in 2010
Havelaar AH , Kirk MD , Torgerson PR , Gibb HJ , Hald T , Lake RJ , Praet N , Bellinger DC , de Silva NR , Gargouri N , Speybroeck N , Cawthorne A , Mathers C , Stein C , Angulo FJ , Devleesschauwer B . PLoS Med 2015 12 (12) e1001923 Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old-although they represent only 9% of the global population-and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels. |
Methodological framework for World Health Organization estimates of the global burden of foodborne disease
Devleesschauwer B , Haagsma JA , Angulo FJ , Bellinger DC , Cole D , Dopfer D , Fazil A , Fevre EM , Gibb HJ , Hald T , Kirk MD , Lake RJ , Maertens de Noordhout C , Mathers CD , McDonald SA , Pires SM , Speybroeck N , Thomas MK , Torgerson PR , Wu F , Havelaar AH , Praet N . PLoS One 2015 10 (12) e0142498 BACKGROUND: The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization to estimate the global burden of foodborne diseases (FBDs). This paper describes the methodological framework developed by FERG's Computational Task Force to transform epidemiological information into FBD burden estimates. METHODS AND FINDINGS: The global and regional burden of 31 FBDs was quantified, along with limited estimates for 5 other FBDs, using Disability-Adjusted Life Years in a hazard- and incidence-based approach. To accomplish this task, the following workflow was defined: outline of disease models and collection of epidemiological data; design and completion of a database template; development of an imputation model; identification of disability weights; probabilistic burden assessment; and estimating the proportion of the disease burden by each hazard that is attributable to exposure by food (i.e., source attribution). All computations were performed in R and the different functions were compiled in the R package 'FERG'. Traceability and transparency were ensured by sharing results and methods in an interactive way with all FERG members throughout the process. CONCLUSIONS: We developed a comprehensive framework for estimating the global burden of FBDs, in which methodological simplicity and transparency were key elements. All the tools developed have been made available and can be translated into a user-friendly national toolkit for studying and monitoring food safety at the local level. |
National studies as a component of the World Health Organization initiative to estimate the global and regional burden of foodborne disease
Lake RJ , Devleesschauwer B , Nasinyama G , Havelaar AH , Kuchenmuller T , Haagsma JA , Jensen HH , Jessani N , Maertens de Noordhout C , Angulo FJ , Ehiri JE , Molla L , Agaba F , Aungkulanon S , Kumagai Y , Speybroeck N . PLoS One 2015 10 (12) e0140319 BACKGROUND: The World Health Organization (WHO) initiative to estimate the global burden of foodborne diseases established the Foodborne Diseases Burden Epidemiology Reference Group (FERG) in 2007. In addition to global and regional estimates, the initiative sought to promote actions at a national level. This involved capacity building through national foodborne disease burden studies, and encouragement of the use of burden information in setting evidence-informed policies. To address these objectives a FERG Country Studies Task Force was established and has developed a suite of tools and resources to facilitate national burden of foodborne disease studies. This paper describes the process and lessons learned during the conduct of pilot country studies under the WHO FERG initiative. FINDINGS: Pilot country studies were initiated in Albania, Japan and Thailand in 2011 and in Uganda in 2012. A brief description of each study is provided. The major scientific issue is a lack of data, particularly in relation to disease etiology, and attribution of disease burden to foodborne transmission. Situation analysis, knowledge translation, and risk communication to achieve evidence-informed policies require specialist expertise and resources. CONCLUSIONS: The FERG global and regional burden estimates will greatly enhance the ability of individual countries to fill data gaps and generate national estimates to support efforts to reduce the burden of foodborne disease. |
Addressing contact tracing challenges - critical to halting Ebola virus disease transmission
Greiner AL , Angelo KM , McCollum AM , Mirkovic K , Arthur R , Angulo FJ . Int J Infect Dis 2015 41 53-5 OBJECTIVES: Delayed and ineffective contact tracing contributed to the extensive transmission of Ebola virus disease (EVD) in the 2014-2015 West African outbreak. Understanding and addressing the challenges to implementing and managing contact tracing is essential to stopping EVD transmission and preventing large-scale EVD outbreaks in the future. METHODS: Interviews were conducted with United States Centers for Disease Control and Prevention staff members engaged in contact tracing activities in the affected West African countries of Sierra Leone, Guinea, Liberia, Senegal, Nigeria, and Mali from September through December, 2014. Two staff members from each country were interviewed. The five most frequently cited contact tracing challenges were identified. RESULTS: Challenges have been evident in every step of the contact tracing process from implementation to management, including identifying, locating, and enrolling contact-persons, as well as managing personnel and ensuring contact tracing performance. Common themes observed in all the affected West African countries have included fear, stigma, and community misperceptions regarding EVD. Countries that have overcome these challenges, ensuring immediate and comprehensive contact tracing, have been successful in halting EVD transmission. CONCLUSIONS: Addressing challenges to contact tracing implementation and management in the West African EVD outbreak is essential to stopping ongoing transmission. |
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